Ingrid Zitnanova

Oxidative Stress in University Students during Examinations

Mental stress in psychiatric disease and in daily life contributes to oxidative stress in the body. In this study we investigated a connection between possible psychological stress caused by university undergraduate examinations and oxidative stress experienced by our test subjects. Some parameters of oxidative stress (single strand breaks of DNA in lymphocytes, sensitivity to lipid oxidation and antioxidant status) were studied in medical students on the day of the examination (stress condition) and compared with the same parameters obtained from the same students during the term between two examination periods (non-stress condition). The results show that in the stress condition oxidative damage to DNA and sensitivity to lipid oxidation were significantly increased (p<0.05) when compared with the same parameters in “non-stress” conditions. A significant decrease in plasma antioxidant activity (p<0.05) in students that were under stress was observed. These results suggest that during university examinations students are under increased oxidative stress.

Markers of oxidative stress in children with Down syndrome.

Abstract Background: Persons with Down syndrome have increased vulnerability to oxidative stress caused by overexpression of superoxide dismutase, an antioxidant enzyme coded on chromosome 21. Increased oxidative stress may lead to oxidative damage of important macromolecules. We monitored this damage by measuring levels of different biomarkers of oxidative stress (protein carbonyls and 4-hydroxy-2-nonenal), as well as plasma antioxidant capacity, in children with Down syndrome. A total of 20 children with Down syndrome and 18 healthy individuals were recruited for this purpose. Methods: Plasma protein carbonyls were measured using an ELISA technique, 4-hydroxy-2-nonenal was monitored by HPLC and the antioxidant capacity was evaluated using a ferric reducing ability of plasma (FRAP) assay. Results: We found that children with Down syndrome had significantly elevated levels of protein carbonyls compared to healthy controls (p<0.01). Levels of 4-hydroxy-2-nonenal and antioxidant capacity were similar in both groups. Conclusion: Our results on oxidative damage to proteins confirm the assumption of increased oxidative stress in individuals with Down syndrome.

Look into brain energy crisis and membrane pathophysiology in ischemia and reperfusion

Abstract In an ischemic environment, brain tissue responds to oxygen deprivation with the initiation of rapid changes in bioenergetic metabolism to ensure ion and metabolic homeostasis. At the same time, the accelerated cleavage of membrane phospholipids changes membrane composition and increases free fatty acid concentration. Phospholipid breakdown also generates specific messengers that participate in signaling cascades that can either promote neuronal protection or cause injury. The net impact of signaling events affects the final outcome of the stroke. While reoxygenation is a life-saving intervention, it can exacerbate brain damage. Although compromised energy metabolism is restored shortly after reperfusion, alterations in membrane phospholipid composition with subsequent accumulation of lipid oxoderivates are neurotoxic, causing oxidative stress and ischemia–reperfusion (IR) injury. Thus, plasma and mitochondrial membranes are the first responders as well as mediators of IR-induced stress signals. In this review, we focus on ischemia-induced changes in brain energy metabolism and membrane functions as the causal agents of cell stress responses upon reoxygenation. The first part of the review deals with the specificities of neuronal bioenergetics during IR and their impact on metabolic processes. The second part is concentrated on involvement of both plasma and mitochondrial membranes in the production of messengers which can modulate neuroprotective pathways or participate in oxidative/electrophilic stress responses. Although the etiology of IR injury is multifactorial, deciphering the role of membrane and membrane-associated processes in brain damage will uncover new therapeutic agents with the ability to stabilize neuronal membranes and modulate their responses in favor of prosurvival pathways.

Resorcylidene aminoguanidine induces antithrombotic action that is not dependent on its antiglycation activity

There is good evidence supporting the notion that aminoguanidine(AG)-derived compounds prevent glycation/glycooxidation-dependent processes and therefore inhibit late diabetic complications. The aim of the present work was to analyse the antithrombotic action and antiglycation activity of beta-resorcylidene aminoguanidine (RAG) in comparison with another commonly used aminoguanidine (AG)-derived compound, pyridoxal aminoguanidine (PAG). In vitro RAG and PAG prevented exhaustive glycation and glycooxidation of BSA to a similar extent. However, merely RAG showed almost complete binding to sepharose-immobilized heparin, while PAG and other AG derivatives had much poorer affinities. In the model of in vivo thrombosis in Wistar rats with extracorporeal circulation RAG (i.v. 30 mg/kg), but not PAG, produced sustained (2 h) antithrombotic effect, which was abrogated by indomethacin (5 mg/kg) and rofecoxib (1 mg/kg). The 60-day treatment of streptozotocin-diabetic animals with RAG (p.o. 4 mg/kg) significantly decreased plasma concentration of a thromboxane B(2) and reduced whole blood platelet aggregability triggered by ADP or collagen. In conclusion, although RAG and PAG displayed similar antiglycation and antioxidation activities in vitro, only RAG showed antithrombotic activity in vivo that involved activation of COX-2/PGI(2) pathway. Our results indicate that designing novel RAG derivatives with optimal antithrombotic and antiglycation activities may prove useful to treat diabetic complications.

Sex differences in the blood antioxidant defense system in juvenile rats with various genetic predispositions to hypertension

This study investigated the contribution of blood oxidative stress (OS) to the development of hypertension, as well as sex differences in the antioxidant defense system (ADS) in genetic models of hypertension. Nine-week-old normotensive Wistar-Kyoto (WKY) rats, borderline hypertensive rats (BHR) and spontaneously hypertensive rats (SHR) of both sexes were used. Systolic blood pressure (SBP) was determined by tail-cuff plethysmography, the trolox equivalent antioxidant capacity (TEAC) and the concentration of lipid peroxides (LP) were determined in plasma. The activity of the antioxidant enzymes Cu/Zn–superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) was determined in erythrocytes. SBP was significantly elevated in BHR and SHR in both sexes. BHR and SHR males had a higher SBP than the respective females. Sex-dependent differences in the ADS were found only in SHR, in which TEAC, SOD and CAT were significantly higher in males than in females. No differences in TEAC, SOD, CAT and GPx were observed between BHR (males and females) and WKY controls. LP levels were similar in all the groups investigated. Significant positive correlations were observed between SBP and both SOD and CAT. TEAC correlated positively with SOD and LP. As no signs of oxidative damage to lipids were found in young BHR and SHR of either sex, OS in the blood does not seem to be causatively related to the development of hypertension in these rats. However, despite activated antioxidant defenses, the positive correlation between plasma TEAC and LP suggests that oxidative damage is progressing slowly and therefore it seems to be a consequence rather than the cause of hypertension.

Chronic Stress Produces Persistent Increases in Plasma Corticosterone, Reductions in Brain and Cardiac Nitric Oxide Production, and Delayed Alterations in Endothelial Function in Young Prehypertensive Rats

This study was designed to investigate whether oxidative stress, nitric oxide (NO) deficiency and/or endothelial dysfunction (ED) are present in young borderline hypertensive rats (BHR) and whether these pathologies can be causally involved in the initiation of blood pressure (BP) increases. Additionally, we tested the hypothesis that crowding stress, experienced during the peripubertal period, may produce persistent or delayed disorders in corticosterone release, NO synthesis, oxidative status and/or endothelial function that could accelerate BP increases. To test these hypotheses, 5-week-old male BHR and normotensive Wistar-Kyoto rats (WKY) were either kept in control conditions (for 2 and 4 weeks, respectively) or exposed to social stress produced by crowding for 2 weeks (stress). After cessation of crowding, a group of rats of each phenotype was kept in control conditions for the next 2 weeks (post-stress). Systolic BP of 5-week-old BHR was significantly increased vs. age-matched WKY (127 ± 3 vs. 104 ± 3 mmHg, p < 0.01) and remained significantly higher throughout the course of the experiment. Despite elevated BP, no signs of oxidative damage to plasma lipids, NO deficiency or ED were observed in control BHR vs. age-matched WKY. Crowding stress elevated plasma corticosterone and accelerated BP increases only in BHR; these effects persisted 2 weeks post-stress. Crowding failed to induce oxidative damage to plasma lipids in either phenotype, but it produced persistent decreases in NO production in the hypothalamus and brainstem of both strains of rats, as well as in the hearts of BHR. In contrast, crowding failed to reduce NO production in the aortae or acetylcholine-induced relaxations of the femoral arteries in both strains investigated. However, significantly reduced aortic NO production was observed in BHR 2 weeks post-stress vs. age-matched controls, which was in agreement with reduced NO-dependent components of vasorelaxation. In conclusion, this study’s data showed that oxidative stress, NO deficiency and ED are not causally involved in initiation of blood pressure increase in BHR. However, exposure to stressful environments produced persistent increases in plasma corticosterone and reductions of brain and cardiac NO production followed by a delayed decrease in the NO-dependent component of endothelium-dependent relaxation—changes that collectively accelerated BP increases only in BHR.